DESC:The following specification particularly describes the invention and the manner in which it is to be performed.

INTRODUCTION
Aspects of the present application relates to co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid and its process.
The drug compound having the adopted name “Apalutamide” has chemical name: 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-methylbenza-mide as below.

US8445507B2 discloses apalutamide or a pharmaceutically acceptable salt thereof, method for treating prostrate cancer using apalutamide or a pharmaceutically acceptable salt thereof and pharmaceutical composition thereof. US9884054B2 discloses method of treating non-metastatic castration-resistant prostate cancer with apalutamide.
US9481663B2 discloses crystalline Form B of apalutamide. US9994545B2 discloses crystalline Form A of apalutamide. US20180258067 A1 discloses crystalline Form C, Form D, Form E, Form F, Form G, Form H, Form I and Form J of apalutamide. WO2016124149A1 discloses crystalline Form I and Form II of apalutamide. WO2016090098A1 discloses solid dispersion of apalutamide with HPMCAS. WO2016090101A1 discloses solid dispersion of apalutamide with a poly(meth)acrylate copolymer. WO2016090105A1 discloses solid dispersion of apalutamide with a poly(meth)actylate copolymer and HPMCAS.
The physicochemical properties of a solid form is a critical parameter in the development of pharmaceutical dosage forms and these properties can affect the bioavailability, stability and processability of the active pharmaceutical ingredient. It is known that a solid active pharmaceutical ingredient can exist in amorphous, crystalline, co-crystal state.
The discovery of new form of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, storage stability, and ease of purification. Accordingly, the present inventors have found new co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid having enhanced storage, stability, solubility and processability.

SUMMARY
In an aspect, the present application provides co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12), characterized by a PXRD pattern comprising the peak at about 11.49°, 28.48° and 29.0°± 0.2° 2?.
In another aspect, the present application provides process for the preparation of co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12) comprising the steps of:
a) dissolving apalutamide and 2, 5 dihydroxy benzoic acid in suitable solvent; and
b) isolating the co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid.

BRIEF DESCRIPTION OF THE DRAWING
Figure 1 is an illustrative X-ray powder diffraction pattern of co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12) prepared by the method of Example No 1.
DETAILED DESCRIPTION
In an aspect, the present application provides co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12), characterized by a PXRD pattern comprising the peak at about 11.49°, 28.48° and 29.0°± 0.2° 2?.
In an embodiment, the application provides co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12), characterized by a PXRD pattern having one or more additional peaks at about 7.02° 9.28°, 14.05°, 14.39°, 18.23° and 24.76°°± 0.2° 2?.
In another embodiment, the application provides co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12), characterized by a PXRD pattern of figure 1.
In another aspect, the present application provides process for the preparation of co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid comprising the steps of:
a) dissolving apalutamide and 2, 5 dihydroxy benzoic acid in suitable solvent; and
b) isolating the co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid.
Any physical form of apalutamide may be utilized for dissolving the solution of apalutamide in step a). Apalutamide that may be used as the input for the process of the present invention may be obtained by the processes described in the art. For example apalutamide may be prepared by the processes described in US8445507B2 and US8987452B2.
In an embodiment of step a), the suitable solvent may be selected from acetonitrile, methanol, ethanol, 2-propanol, 1-butanol, 2-butanol, 1-pentanol, 2-pentanol, 3-pentanol, dichloromethane, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl acetate, ethyl acetate, isopropyl acetate, tetrahydrofuran, and mixtures thereof.
In an embodiment, providing a solution at step a) may be carried out by taking the reaction mixture containing apalutamide and 2, 5 dihydroxy benzoic acid in a suitable solvent simultaneously or by dissolving components in a suitable solvent separately to form individual solutions and combining those solutions later.
In an embodiment, a solution of apalutamide and 2, 5 dihydroxy benzoic acid may be prepared at any suitable temperatures, such as about 0°C to about the reflux temperature of the solvent used. Stirring and heating may be used to reduce the time required for the dissolution process. In specific embodiment, a solution of apalutamide and 2, 5 dihydroxy benzoic acid may be prepared at about 75°C.
In an embodiment, a solution of apalutamide and 2, 5 dihydroxy benzoic acid may be filtered to make it clear, free of unwanted particles. In embodiments, the obtained solution may be optionally treated with carbon, to remove colored components, etc., before filtration.
In an embodiment of step b), the reaction mixture of apalutamide may be cooled to about 25°C to precipitate the solid.
In an embodiment of step b), the isolation of co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12) may be carried out by any methods known in the art or procedures described in the present application. In an embodiment, co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12) may be isolated by employing any of the techniques, but not limited to: filtration by gravity or suction, decantation, centrifugation, adding solvent to make slurry followed by filtration, or other techniques specific to the equipment used and the like, and optionally washing with a solvent.
In specific embodiment of step b), the isolation of co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12) may be carried out by filtration under vacuum.
Co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12) isolated at step b) may be dried in a suitable drying equipment such as tray dryer, vacuum oven, rotatory cone dryer, air oven, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying may be carried out at atmospheric pressure or under reduced pressures at temperatures of less than about 100°C, less than about 60°C, or any other suitable temperatures. The drying may be carried out for any time period required for obtaining a desired quality, such as from about 15 minutes to 10 hours or longer.
The ratio of apalutamide to 2, 5 dihydroxy benzoic acid may be stoichiometric or non-stoichiometric according to the present invention. For example, 1:1, 1:1.5 and 1:2 ratios of apalutamide: 2, 5 dihydroxy benzoic acid are acceptable.
The present application provides co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12) having a chemical purity of atleast 99% by HPLC or atleast 99.5% by HPLC or atleast 99.9% by HPLC.
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following example, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Variations of the described procedures, as will be apparent to those skilled in the art, are intended to be within the scope of the present application.
DEFINITIONS
The term "about" when used in the present application preceding a number and
referring to it, is meant to designate any value which lies within the range of ±10%,
preferably within a range of ±5%, more preferably within a range of ±2%, still more
preferably within a range of ±1 % of its value. For example "about 10" should be
construed as meaning within the range of 9 to 11 , preferably within the range of 9.5
to 10.5, more preferably within the range of 9.8 to 10.2, and still more preferably
within the range of 9.9 to 10.1.
The term “co-crystal” as used herein means a crystalline material comprised of two or more unique solids at room temperature, each containing distinctive physical characteristics, such as structure, melting point and heats of fusion. The co-crystals of the present invention comprise a co-crystal former H-bonded to an API.

Example-1: Preparation of co-crystal of apalutamide and 2, 5 dihydroxy benzoic acid (VK12).
Apalutamide (2 g) and 2, 5 dihydroxy benzoic acid (2 g) were dissolved in acetonitrile (20 mL) at 75°C. The obtained clear solution was cooled to 25°C. The resulting slurry was filtered under vacuum at 25°C to obtain the title compound.
,CLAIMS:We claim:
1. A crystalline form of apalutamide characterized by a PXRD pattern comprising the peaks at about 11.49°, 28.48° and 29.0°± 0.2° 2?.
2. The process for the preparation of crystalline form of apalutamide as claimed in claim 1, the process comprising the steps of:
a) dissolving apalutamide in organic solvent; and
b) isolating the crystalline form of apalutamide.
3. The process for the preparation of crystalline form of apalutamide as claimed in claim 2, wherein the organic solvent is selected from acetonitrile, methanol, ethanol, 2-propanol, 1-butanol, 2-butanol, 1-pentanol, 2-pentanol, 3-pentanol, dichloromethane, acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl acetate, ethyl acetate, isopropyl acetate, tetrahydrofuran or mixtures thereof.